טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentUnger Rozalia
SubjectZn-Brook Rearrangement in Carbocyclization Reaction
DepartmentDepartment of Chemistry
Supervisor Professor Ilan Marek
Full Thesis textFull thesis text - English Version


Abstract

The construction of carbon-carbon bonds is undoubtedly one of the most important operations in organic chemistry, and among them formation of carbocycles. Reactions which result in the addition of a carbon-metal bond of an organometallic across a carbon-carbon multiple bond, leading to a new organometallic in which the newly formed carbon-metal bond can be used for further synthetic transformation, are called carbometalation reactions. If the carbometalation reaction is performed on an asymmetrically substituted double bond, two new sp3 stereogenic centers are created after reaction with an electrophile. Thus, in order to have a powerful reaction, it is necessary to control the regio- and diastereoselectivity of this carbometalation reaction.

In this research we wanted to explore the carbometalation reaction of delocalized organometalics across unactivated unsaturated systems; to focus on the construction of polysubstituted carbocycles by reaction of alkynylmetal derivatives to several acylsilanes followed by the tandem Brook-rearrangement and intramolecular carbocyclization for the formation of five-membered rings.

The intramolecular 1,2-migration of a silyl group from a carbon atom to an oxygen atom was originally recognized and studied by Brook in the late 50s. However, in order to have an efficient silyl migration, in-situ addition of an electrophile was necessary to maximize the yield of the Brook rearrangement.

During our studies, we have found that ZnBr2 can be used successfully as an electrophile to shift quantitatively the equilibrium of the Brook rearrangement. We have been able to use this rearrangement for the ene-allene carbocyclization reaction.  When alkynylmagnesium derivatives are added to acylsilane, magnesium alcoholate are obtained quantitatively.  However, even after an extended period of time, the Brook-rearrangement was not observed in a significant amount.

In contrast, when ZnBr2 was added to the reaction mixture, the rearrangement occurs to give first the corresponding zinc alcoholate, which subsequently undergoes the rearrangement into the allenylzinc species.  After stirring for few hours, cyclic product was obtained in good yield and as a unique geometric isomer for the creation of a tertiary and quaternary stereogenic centers.

More recent investigations have shown that this method can lead to enantiomerically enriched carbocycles via asymmetric catalysis. In this case alkynylzinc derivatives are added to acylsilanes in the presence of chiral ligands to lead to zinc alcoholates which rearrange to propargyl/allenyl zinc species quantitatively. After stirring for several hours, cyclic products are obtained in excellent yields and as a unique diastereoisomer and in good enantioselectivity.